Differential Effects of LPS and 6-OHDA on Microglia’s Morphology in Rats: Implications for Inflammatory Model of Parkinson’s Disease
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Pars compacta
MPTP
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Neuromelanin
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Objective:To observe the characteristic changes of FA value of substantia nigra pars compacta in early Parkinson′s disease using 1.5T MR scanner.Methods:20patients with early Parkinson′s disease and 28cases of gender and age-matched normal volunteers had MR scanning with T2WI sequence and DTI.Taking T2WI as reference,hand-sketched region of interest(ROI)including head,body,tail as well as internal and external areas in substantia nigra were done,their FA values were measured.Statistical analysis was calculated.Results:FA values of substantia nigra pars compacta decreased significantly in early Parkinson′s disease;The FA values of the head,body,tail of substantia nigra pars compacta were lower than those of the normal control group significantly,with the head as the most obvious,which was 0.201±0.030and 0.254±0.050respectively,P0.05.When FA value of the head of substantia nigra pars compacta was less than 0.224, Parkinson′s disease should be highly suspected.Conclusion:Lowering of FA values of the head of substantia nigra pars compacta shows a certain value in the early diagnosis of Parkinson′s disease.
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to define the quantitative characteristics of cell structures in the substantia nigra pars compacta of neurologically healthy elderly people (men and women).Autopsy brain materials from neurologically healthy men and women who had died from intercurrent diseases at the age of 72 to 87 years were examined for quantitative characteristics of the substantia nigra pars compacta, by applying computed morphometric methods.In the elderly people (men and women), the compactness of arrangement of neurons, including those containing tyrosine hydroxylase (a marker of dopamine neurons), was much higher and the glial index was lower in the ventral area of the substantia nigra pars compacta than in the dorsal area. Comparing the structures in the substantia nigra pars compacta showed that the neurons were larger in the dorsal area and the variability of the compactness of their arrangement and the glial index were higher in the women than in the men.In the elderly people, the cell structures in the substantia nigra pars compacta are typified by high morphometric heterogeneity.Цель - определение количественных характеристик клеточных структур компактной части черной субстанции мозга неврологически здоровых лиц (мужчин и женщин) пожилого возраста. Материал и методы. На аутопсийном материале мозга неврологически здоровых мужчин и женщин, умерших от интеркуррентных заболеваний в возрасте от 72 до 87 лет, изучали количественные характеристики клеточных структур компактной части черной субстанции, используя методы компьютерной морфометрии. Результаты. У лиц пожилого возраста (мужчин и женщин) в вентральной области компактной части черной субстанции плотность расположения нейронов, в том числе содержащих тирозингидроксилазу (маркер дофаминовых нейронов), значительно выше, а глиальный индекс - ниже, чем в дорсальной области. Сопоставление структур компактной части черной субстанции мозга мужчин и женщин показало, что по сравнению с мужчинами у женщин в дорсальной области нейроны крупнее, а вариабельность показателя плотности их расположения и величина глиального индекса выше, чем у мужчин. Заключение. Для клеточных структур компактной части черной субстанции мозга лиц пожилого возраста характерна высокая морфометрическая гетерогенность.
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Increasing evidence suggests a pivotal role for neuroinflammation in the pathogenesis of Parkinson disease, but whether activated microglia participate in disease progression remains unclear. To clarify this issue, we determined the numbers of activated microglial cells in the substantia nigra pars compacta and ventral tegmental area of monkeys subacutely and chronically exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Monkeys in the subacute MPTP treatment group were killed 1 week after the last MPTP injection; chronically treated monkeys were killed either 6 or 35 months after the last MPTP injection. Subacute MPTP administration induced loss of dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area and microglial activation in the same areas. Chronic MPTP treatment resulted in greater dopaminergic neuron depletion in both treatment groups. Both groups of chronic MPTP-treated monkeys showed increased numbers of activated microglial cells in the substantia nigra pars compacta that were similar to those of the subacute MPTP treatment group. These results indicate that microglial activation seems to be induced mainly by the toxic effects of MPTP and that it does not further progress once the toxin administration has been terminated. This suggests that the progressive degeneration of nigral cells in Parkinson disease may not necessarily be associated with progressively increased microglial activation.
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Background. Up to the moment there is no universally accepted scheme of spatial organization of the groups of neurons of substantia nigra pars compacta of the human midbrain. A detailed study of the architectonics of this structure is necessary for pathomorphological analysis of agerelated changes in the nervous tissue and the associated neurodegenerative diseases with selective death of dopamine neurons.
Aim. To clarify the peculiarities of the morphochemical organization of the substantia nigra (SN) of a human brain and to create a threedimensional model of pars compacta.
Materials and Methods. Threedimensional reconstruction of substantia nigra pars compacta was performed on the brain autopsy material of individuals without neurological pathology (n=10, between 52 to 84 years of age) using a method of computed morphometry. Sections of the midbrain were stained by Nissl method and by an immunohistochemical method for localization of tyrosine hydroxylase – a marker of dopamine.
Results. In the SN pars compacta accumulations of neurons were identified in the form of 9 bands oriented in the rostrocaudal direction and including four areas: medial, lateral, dorsal and ventral. Morphometric analysis detected significant differences in the density of neurons and in expression of tyrosine hydroxylase between the areas of SN.
Conclusion. A model of cellular organization of SN pars compacta proposed by us on the basis of threedimensional reconstruction is characterized by a high degree of detalization as compared to similar works, and shows expressed spatial differentiation of the groups of neurons of SN which should be taken into consideration in pathomorphological examinations.
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During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder of this system, Parkinson's disease, is characterized by a selective, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. This review includes studies quantifying age and Parkinson's-related changes of the substantia nigra, with emphasis on stereological studies performed in the substantia nigra pars compacta.
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Dysfunction of the ubiquitin-proteasomal system (UPS) has been implicated in the pathogenesis of Parkinson's disease. The systemic administration of UPS inhibitors has been reported to induce nigrostriatal cell death and model Parkinson's disease pathology in rodents. We administered a synthetic, specific UPS inhibitor (PSI) subcutaneously to rats and quantified substantia nigral tyrosine hydroxylase-positive dopaminergic neurons by stereology. PSI caused a 15% decrease in UPS activity at 2 weeks and a 42% reduction in substantia nigra pars compacta tyrosine hydroxylase-positive neurons at 8 weeks. Systemic inhibition of the UPS warrants further evaluation as a means to model Parkinson's disease.
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Pathogenesis
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